1
Information and genetic counselling for psychiatric risks in children with rare genomic
disorders
Andrew Cuthbert, PhD, MSc1, Aimee Challenger, BSc2, Jeremy Hall, MRCPsych, PhD*3, and
Marianne BM van den Bree, PhD*1
Affiliations
1MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological
Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK
2School of Psychology, Cardiff University, Cardiff, UK.
3Neuroscience and Mental Health Research Institute, Division of Psychological Medicine and
Clinical Neurosciences, Cardiff University, Cardiff, UK
Corresponding author: Marianne BM van den Bree PhD, Telephone: +44 (0)2920 688433,
email [email protected]
*J Hall and M van den Bree contributed equally to the work.
Contributors
A Challenger (ACh), M van den Bree (MvdB) and J Hall (JH) conceived the research
question and designed the study. ACh developed the study ethics application. A Cuthbert
(ACu) and ACh oversaw recruitment of study participants and data acquisition. ACu oversaw
and conducted all data analysis and interpretation. ACu, JH and MvdB reviewed and
discussed and revised the data analysis. ACu drafted the manuscript, figures and tables. All
authors provided critical revisions to the manuscript, intellectual content and final approval for
submission.
. CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted September 25, 2019. .https://doi.org/10.1101/19007294doi: medRxiv preprint
2
Abstract
Purpose: Genomic medicine has transformed the diagnosis of neurodevelopmental
disorders. Evidence of increased psychiatric comorbidity associated with genomic copy
number and single nucleotide variants (CNV and SNV) may not be fully considered when
providing genetic counselling. We explored parents’ experiences of genetics services and
how they obtained information concerning psychiatric manifestations.
Methods: Parents of children diagnosed with genomic variants completed an online survey
exploring, (i) how they experienced the genetic diagnosis, and (ii) how they acquired
information about psychiatric, developmental and physical manifestations.
Results: Two-hundred and 86 respondents completed the survey. Thirty percent were
unsatisfied with receiving genetic diagnoses. Satisfaction was predicted if communication
was by geneticists (p = 0.004); provided face-to-face (p = 0.003); clearly explained (p <
0.001); and accompanied by support (p = 0.017). Parents obtained psychiatric information
from non-professional sources more often than developmental ( 0.26, p < 0.001) and
physical manifestations ( 0.21, p = 0.003), which mostly came from health professionals.
Information from support organisations was more helpful than from geneticists (odds ratio
[OR] 21.0, 95% CI 5.1 – 86.8, p < 0.001); paediatricians (OR 11.0, 1.4 – 85.2, p = 0.004);
and internet sites (OR 15.5, 3.7 – 64.8, p < 0.001).
Conclusion: A paucity of professional information about psychiatric risks after genetic
diagnosis may impede early diagnosis and intervention for children with high genotypic risks.
Planned integration of genomic testing into mainstream services should include genetic
counselling training to address the full spectrum of developmental, physical and psychiatric
manifestations and timely provision of high-quality information.
. CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted September 25, 2019. .https://doi.org/10.1101/19007294doi: medRxiv preprint
3
Key words: Genetic counselling, copy number variants, CNVs, psychiatry,
neurodevelopmental disorders, mental health, patient information.
. CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted September 25, 2019. .https://doi.org/10.1101/19007294doi: medRxiv preprint
4
INTRODUCTION
Approximately 1 in 25 children in high income countries have neurodevelopmental disabilities
(ND).[1] Clinical evaluation may include genetic investigations, which for many individuals
can improve diagnostic accuracy, guide appropriate interventions and enhance genetic
counselling for the family. Technological barriers to identifying genetic causes in severely
disabled children have substantially diminished since the mid 2000s with the introduction of
genome-wide diagnostic tests, primarily chromosomal microarray (CMA) assays capable of
detecting sub-microscopic genomic imbalances known as Copy Number Variants (CNVs).
Numerous genomic variants including CNVs and single nucleotide variants (SNVs) have
been associated with ND and co-occurring psychiatric phenotypes.[2–4] For example, the
3Mb CNV diagnosed in 22q11.2 Deletion Syndrome (formerly Velocardiofacial Syndrome
and DiGeorge syndrome) is causally associated with high rates of autism spectrum disorder
(ASD), ADHD, schizophrenia, oppositional defiant disorders and anxiety.[5–7) Collectively, ND
associated CNVs are implicated in up to 15% of children with severe developmental
disorders who access genomic medicine services.[[8] Estimates suggest up to 42% of
undiagnosed developmental disorders (DD) are due to de novo mutations in coding
sequences about which risks for psychiatric complications are less well understood.[[9]
Variation in the penetrance of genomic variants associated with ND,[10–12] suggests health
outcomes are susceptible to socio-environmental modification, additional undetected
mutations and polygenic variation, presenting significant barriers to personalisation of
medicine, genetic counselling and family-oriented information. However, genomic diagnosis
is recognised as a major advantage to individuals with rare developmental disorders.[13,14]
Progress towards introducing increasingly sophisticated whole genome and exome
sequencing into clinical services is, however, placing additional demands on practitioners in
terms of additional training requirements, clinic time, informed consent, and information
provision.[15–17] The complexity of neurodevelopmental, physical and psychiatric outcomes
associated with deleterious genomic variants presents important challenges for practitioners
. CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted September 25, 2019. .https://doi.org/10.1101/19007294doi: medRxiv preprint
5
confronted by parents requiring detailed information about their child’s future health and
wellbeing.[18–20]
The design and implementation of genomics medicine services for a broader range of
neurodevelopmental conditions should account for the views and opinions of service users
and recognise the need for relevant information both before and after genetic investigations.
In this study we sought to address these issues by, (i) identifying key factors influencing
parental satisfaction with genetics services, specifically the communication of diagnostic
variants by clinical specialists; (ii) exploring how parents gain knowledge of developmental,
psychiatric and physical manifestations of genomic variants; and (iii) comparing the
availability, content and helpfulness of patient information obtained from health professionals,
internet sites, voluntary support groups and other sources.
METHODS
Survey respondents and procedures
We designed a 46 item online survey, using Online Surveys
(https://www.onlinesurveys.ac.uk, Jisc, Bristol UK), for parents of children aged 0-17 years
with developmental, intellectual and congenital disorders having a clinical genetic diagnosis.
The survey comprised 4 main sections: (1) family demographics, child’s genotype, reported
medical, developmental and psychiatric diagnoses, family genetic history; (2) awareness of
manifestations associated with child’s genetic diagnoses and sources of information to
understand them; (3) ratings of the quantity, content and helpfulness of information from; and
(4) experiences of services and receiving genetic test results. An introductory section
included information about the research team, the purpose of the study, instructions for
participating, participant confidentiality and data protection. Participants provided consent by
agreeing with the statement, “I have read the information above and on the previous page,
. CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted September 25, 2019. .https://doi.org/10.1101/19007294doi: medRxiv preprint
6
understand that my participation is voluntary, and I am happy to complete the questionnaire”.
The study received ethical approval from Cardiff University School of Medicine Ethics
Committee on 19 September 2014 (reference SMREC 14/34). Invitations to take part were
distributed by advertisements in newsletters, websites and Facebook pages and by word-of-
mouth at family support days sponsored by rare disorders support groups, including Unique
– Understanding Rare Chromosome and Gene Disorders, Max Appeal, and Microdeletion
16p11.2 Support and Information UK.
Statistical analyses
Response data was coded and downloaded from the survey website into the SPSS package
(IBM Corp. SPSS Statistics for Mac, version 25.0, Armonk, NY, 2017) for statistical analysis.
For identification of factors which influence parental satisfaction with genetics services we did
logistic regression. We designed a hierarchical model including variables covering, (i)
demographic data; (ii) components of genetic counselling process; and (iii) health providers
involved in communicating results. The binary outcome variable was defined as parental
satisfaction (or dissatisfaction) with the communication of diagnostic genetic test results by
their health provider. The initial regression model incorporated family and child specific
covariate using method ‘Enter’. Sequential hierarchical models incorporated genetic
counselling and communication modality specific covariates. Where appropriate, ordinal
variables were collapsed into fewer categories where responses were low. Odds ratios
correspond to the exponentiated unstandardised coefficients (beta weights) for each
variable. We employed a variety of tests to explore (a) sources of and (b) relative merits of
information received by families after genetic testing. To compare information sources
reported we used chi-square analyses of 2x2 contingency tables to examine relationships
between 4 categories of manifestation, (i) developmental, (ii) physical, (iii) neuropsychiatric
and (iv) other psychiatric disorders. Effect sizes were described in terms of Cramer’s phi
coefficients (). Pairwise comparisons of information sources between individual
manifestations was done by McNemar’s chi-square tests for marginal homogeneity in
. CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted September 25, 2019. .https://doi.org/10.1101/19007294doi: medRxiv preprint
7
matched-pair binomial data. Odds ratios were calculated with VassarStats at
http://www.vassarstats.net. To explore the relative quantity and quality of data from different
sources we employed Wilcoxon’s signed-rank test to compare Likert scale responses and
derived effect sizes (r) from Z scores.
RESULTS
Respondents
Two-hundred and eighty-six survey responses were recorded between 12 December 2014
and 31 May 2017. 199 respondents (70%) were located in the UK and 87 (30%) in the USA.
Table 1 shows details of the respondents and their children. The most frequent reasons for
referral to genetics services were developmental delay (N= 98, 34.4%), congenital anomaly
(12.2%) and dysmorphic features (N=21, 7.3%). In addition to the referral indication for
genetic testing, parents reported their children had multiple developmental, physical,
neuropsychiatric and other mental health manifestations, a mean of 5.7 diagnoses. In terms
of genetic diagnoses, 243 (85%) were diagnosed with chromosomal copy number variants
(CNVs) which reportedly explained the referral. Of the CNVs reported, 116 (40.6%) were loci
significantly associated with neurodevelopmental and psychiatric outcomes. Sixteen (5.6%)
children had more than 1 CNV and 22 (7.7%) were diagnosed with single nucleotide variants
(SNV) of which 5 were eponymous genetic syndromes. Thirty-nine parents (13.6%) reported
their child’s CNV was inherited.
Respondents Children Parent reported diagnoses
Location N % Age (years) Mean Range Clinical N Mean
UK 199 69.9 Age when diagnosed 3.7 0-17 Developmental1 695 2.4
USA 87 30.4 At time of survey 8.5 0-42 Physical2 638 2.2
Gender N % Gender N % Neuropsychiatric3 230 0.8
Female 270 94.4 Female 125 43.7 Mood and Psychotic4 80 0.3
Male 16 5.6 Male 161 56.3 Total 1643 5.7
. CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted September 25, 2019. .https://doi.org/10.1101/19007294doi: medRxiv preprint
8
Relationship N % Reason for referral N % Genetic data N %
Biological parent 267 93.3 Developmental delay 98 34.3 Neurodevelopmental CNV5 116 40.6
Adoptive parent 10 3.5 Congenital anomaly 35 12.2 Other CNV 127 44.4
Legal guardian 2 0.7 Dysmorphic features 21 7.3 Multiple CNVs 16 5.6
Other 7 2.4 Growth or stature 16 5.6 Named gene 17 5.9
Occupation N % Neurological 16 5.6 Named syndrome 5 1.7
Employed 141 49.3 Multiple concerns 13 4.5 Unspecified 5 1.7
Carer 78 27.3 Learning disability 11 3.8 Total 286 100
Home maker 58 20.3 Family history 10 3.5 Inherited CNV 39 13.6
Other 9 3.1 Neurodevelopmental 10 3.5 Siblings with CNV 20 7.0
Neonatal concerns 9 3.1 Other relatives with CNV 13 4.5
Foetal anomaly 7 2.4
Metabolic 2 0.7
Unspecified 38 13.3
Table 1. Characteristics of the study sample. 1 Developmental Delay, Learning Disability, Speech and
Language Delay. 2 Palatal, Cardiac, Respiratory, Musculoskeletal, Growth, Seizures/epilepsy, Sight,
Hearing, Skin. 3 Attention deficit hyperactivity disorder, ADHD (N= 47), autism spectrum disorder, ASD
(N= 86), obsessive compulsive disorder, OCD (N = 48), developmental coordination disorder, DCD (N
= 49), dyslexia (N = 19). 4 Anxiety, Depression, Schizophrenia or psychosis. 5 Neurodevelopmental
CNVs: 1q21.1 deletion, 1q21.1 duplication, 2p16.3 deletion (NRXN1), 9q34.3 deletion, 15q11.2
deletion, 15q11.2 duplication, 15q11.2 (NOS), 15q13.3 deletion, 15q13.3 duplication, 15q13.3 (NOS),
16p11.2 deletion, 16p11.2 duplication, 16p11.2 (NOS), 16p12.2 deletion, 16p13.11 deletion, 16p13.11
duplication, 16p13.11 (NOS), 17q12 deletion, 22q11.2 deletion, 22q11.2 distal deletion, 22q11.2
duplication.
Reporting genetic diagnoses for developmental disorders
The great majority of respondents received their child’s genetic test result from paediatricians
(130/286, 45.5%), clinical geneticists (116/286, 40.6%) or genetic counsellors (28/286,
9.8%). Parents were more likely to receive results from paediatricians than genetic
specialists in the UK (107 vs 81) compared to those in the USA (22 vs 63, p <0.001). Eighty-
. CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted September 25, 2019. .https://doi.org/10.1101/19007294doi: medRxiv preprint
9
five of 286 respondents (29.7%) were dissatisfied with how their child’s test result was
communicated. Parents in the UK were more likely to be dissatisfied than in the USA (66/199
vs 19/87; p = 0.05). In terms of the specialism of health professionals delivering results,
parents significantly were more likely to be satisfied when genetic specialists delivered
results (116/144, 80.6%) as compared to paediatricians (78/129, 60.5%; p <0.001), which
was accounted for by UK responses (figure 1 upper panel). More than one-in-three (101/286,
35.3%) were not satisfied with the explanation of their child’s genetic findings. Dissatisfaction
was more prevalent among UK than USA respondents (78/199 vs 23/87, p = 0.038). Again
parents were more likely to be satisfied by explanations given by genetic specialists than by
paediatricians (106/144 vs 70/129, p = 0.001), which was also accounted for by UK
responses (figure 1 lower panel). Around 3-in-10 parents (90/286, 31.5%) did not receive
supporting information to accompany test results, which was more prevalent among UK
respondents (36.2% vs 20.7%, p = 0.009). Almost three quarters of parents (208/286,
72.7%) reported not receiving support when test results were given, half (142/286, 49.7%)
were not offered follow-up appointments.
We used logistic regression to identify predictive factors for satisfaction with receiving genetic
test results, incorporating 3 categories of variables; (i) child and family specific; (ii) genetic
counselling; and (iii) modes of communication. A hierarchical model revealed satisfaction
was most likely if, (i) results were presented by genetic specialists rather than paediatricians
(OR = 2.97, CI 1.41–6.26); (ii) results were communicated in person instead of letter or
telephone call (OR = 2.91, CI 1.41–6.26); (iii) results were satisfactorily explained (OR =
5.14, 95% CI 2.58–10.26); and (iv) support was given at the same time (OR = 2.99 CI 1.21–
7.36). Interestingly, parents of children identified as male were substantially more likely to be
satisfied than those with females (final model OR = 2.56, CI 1.28–5.14). Receiving
supplementary information from the practitioner or a follow-up appointment did not predict
satisfaction. The final model accounted for 40.5% of the variance in the outcome variable
(see Table in supplementary information).
. CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted September 25, 2019. .https://doi.org/10.1101/19007294doi: medRxiv preprint
10
Sources of information on genomic disorders
We asked parents to indicate which sources they had used to gather information concerning
manifestations associated with their child’s genetic variant, (i) health professionals; (ii)
internet sites; (iii) voluntary sector support groups; and (iv) other lay sources (friends and
family, books, leaflets and other materials). We compared sources used between 4 groups of
manifestations, (i) developmental disorders; (ii) physical anomalies; (iii) neuropsychiatric
disorders; and (iv) mood and psychotic disorders (defined in table 2). Information on
developmental disorders was more likely to be given by health professionals at the time of
genetic diagnosis or at follow-up compared with neuropsychiatric disorders (60.7% vs
37.9%), for which a majority parents used alternative sources (Cramer’s 0.22, p < 0.001).
The disparity increased when comparing developmental disorders with mood and psychotic
manifestations (60.7% vs 28.6% used health professional sources, ( 0.29, p < 0.001) but
not physical anomalies (table 2). Overall, fewer parents were informed about mental health
manifestations 34.7% than developmental and physical manifestations (59%) by their
clinician after genetic diagnosis as opposed to finding information from other sources, (
0.24, p <0.001). Following genetic diagnosis, fewer than 1-in-3 parents received information
from their child’s Clinician about the possibility of mood and psychotic disorders (table 2).
. CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted September 25, 2019. .https://doi.org/10.1101/19007294doi: medRxiv preprint
11
Developmental and physical manifestations Mental health manifestations
Information source Developmental Physical Combined Neuropsychiatric Mood + psychotic Combined
N %1 N %1 N %1 N %1 N %1 N %1
Health professional
With diagnosis 318 39.8 149 35.2 467 38.2 121 20.6 45 14.2 166 18.3
At follow-up 70 8.8 38 9.0 108 8.8 38 6.5 12 3.8 50 5.5
Other 96 12.0 49 11.6 145 11.9 64 10.9 34 10.7 98 10.8
Total 484 60.7 236 55.8 720 59.0 223 37.9 91 28.6 314 34.7
Non-professional
Internet sites 167 20.9 103 24.3 270 22.1 163 27.7 106 33.3 269 29.7
Support groups 74 9.3 40 9.5 114 9.3 100 17.0 66 20.8 166 18.3
Other sources 73 9.1 44 10.4 117 9.6 102 17.3 55 17.3 157 17.3
Total 314 39.3 187 44.2 501 41.0 365 62.1 227 71.4 592 65.3
Total observations 798 423 1221 588 318 906
Table 2. Sources of information reported by parents concerning manifestations of their child’s genetic diagnosis. Totals for each group of manifestations
comprise cumulative frequencies for individual conditions: (1) Developmental = global developmental delay (N=274), intellectual disability (N=267), speech
and language delay (N=257); (2) Physical = cardiac defects (N=153), palatal defects (N=97), seizures/epilepsy (N=166); (3) Neuropsychiatric = autism
spectrum disorder (N=203), attention deficit hyperactivity disorder (N=130), obsessive compulsive disorder (N=140), developmental co-ordination disorder
(N=115); (4) Mood and psychotic = anxiety (N=154), depression (N=85), schizophrenia or psychosis (N=73). Figures in parenthesis are counts for parent-
. CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted September 25, 2019. .https://doi.org/10.1101/19007294doi: medRxiv preprint
12
reported associations between their child’s genotype and individual manifestations. 1 percentage values are for cumulative counts for individual
manifestations in each group.
. CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted September 25, 2019. .https://doi.org/10.1101/19007294doi: medRxiv preprint
13
The observation of increased psychiatric co-morbidity in individuals with neurodevelopmental
CNVs (ND-CNVs) [5] prompted us to examine whether clinicians were more likely to offer
information concerning risks for either neurodevelopmental or psychiatric outcomes to
parents of children diagnosed with ND-CNVs (116/248, 46.8% reported CNVs) with,
compared to those with other CNVs (132/248, 53.2%). For neurodevelopmental phenotypes
(DCD, OCD, ADHD and ASD, defined in table 2), combined responses across all
manifestations revealed parents of children with ND-CNVs were more likely to obtain
information from lay sources than from their child’s clinician (Cramer’s 0.13, p = 0.004).
The difference between CNV type was greatest for DCD ( 0.29, p = 0.004). Similarly, for
psychiatric disorders (schizophrenia or psychosis, anxiety and depression), in the event of
receiving ND-CNV diagnoses, parents were more likely to employ lay sources of information
( 0.16, p = 0.01). There were no differences between information sources for developmental
or physical manifestations.
We then compared the main source of information (clinician delivering result versus all other
sources) between individual manifestations parents associated with their child’s genetic
diagnosis. Marginal homogeneity tests of matched pair data compared sources for each
manifestation with reference phenotypes for 3 categories or clinical manifestation: ID
(developmental disorders); cardiac anomalies (physical disorders); and ASD (psychiatric
disorders). Compared to ID, information about all psychiatric manifestation was more likely to
be obtained from sources other than clinicians. Odds ratios (OR) ranged from 2.7 for ASD
(95% CI 1.5 – 4.8, p = 0.001) to 18.0 for depression (CI 2.4 – 134.8, p < 0.001) (figure 3,
upper panel). Other than DD, there were no differences between the main source for ID and
any developmental or physical disorder we tested (figure 2 upper panel). Comparisons with
information sources for cardiac anomalies revealed a similar picture, with ORs ranging from
3.63 for ASD (CI 1.7 – 7.9, p = 0.001) to 31.0 for depression (CI 4.23 – 227.1, p < 0.001)
. CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted September 25, 2019. .https://doi.org/10.1101/19007294doi: medRxiv preprint
14
(figure 2 middle panel). Finally, in comparison to ASD, information about anxiety, depression
and OCD was more likely to be acquired from lay sources, OR range 6.0 for OCD (CI 1.8 –
20.4, p = 0.001) to 16.0 for anxiety (CI 2.1 – 120.7, p < 0.001) (figure 2 lower panel).
Conversely, parents were more likely to be informed about cardiac anomalies,
developmental delay, intellectual disability and speech and language delay by clinicians
rather than obtaining information from other sources. Odds ratios varied between 2.7 for ID
(CI 1.5 – 4.8, p = 0.001) and 12.8 for DD (CI 5.6 – 29.5, p < 0.001).
We explored whether large differences in the speciality of clinicians returning genetic test
results in UK and USA associated with different patterns of information seeking by parents
subsequent to diagnosis. Parents in the USA received more information on developmental
and physical manifestations from health professionals (68.5% professional vs 31.5% other
source) than in the UK (54.3% professional vs 45.7% other, Cramer’s 0.13, p <0.001) (see
figure 3a). Between country differences were larger for psychiatric disorders. For
neuropsychiatric manifestations (ASD, ADHD, OCD), 69.5% of UK parents obtained
information from lay sources compared to 45.3% in the USA ( 0.23, p < 0.001). For mood
and psychotic disorders (anxiety, depression, schizophrenia, psychosis) less than 1-in-5
(19.2%) UK parents obtained information from clinicians, compared to 47.6% in the USA (
0.30, p <0.001, figure 3c). Overall, UK parents sought information alternative sources more
often than their US counterparts (57.6% vs 38.3%, Cramer’s 0.18, p < 0.001, figure 3d).
Finally, we evaluated respondents’ opinions on the quantity, content and helpfulness of
information obtained according to its source. Analysis of mean ranks revealed the amount of
information available from support groups was more optimal than from paediatricians (r 0.47,
p <0.001), geneticists (r 0.51, p <0.001) and internet sites (r 0.38, p <0.001) (table 3).
Similarly, information from internet sites was more optimal than that from paediatricians (r
0.34, p <0.001) and geneticists (r 0.32, p <0.001). In terms of the quality of its content,
information from support groups was more optimal than internet sites (r 0.31, p <0.001),
. CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted September 25, 2019. .https://doi.org/10.1101/19007294doi: medRxiv preprint
15
geneticists (r 0.29, p <0.001) and paediatricians (r 0.14, p = 0.012). In terms of the
usefulness of information, pairwise comparisons revealed that support groups strongly
outperformed internet sites (Odds ratio 15.5, 95% CI 3.71–64.77, p <0.001), paediatricians
(OR 11.0, 1.42–85.2, p = 0.004) and geneticists (OR 21.0, 5.08–86.75, p <0.001), Internet
derived information was more helpful than content given by geneticists (OR 2.5, CI 1.45–
4.32, p = 0.001) but not paediatricians (table 3). Collectively, lay sources of information were
consistently more helpful to parents than information given by health professionals (OR 2.2,
CI 1.37–3.53, p = 0.001, table 3).
. CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted September 25, 2019. .https://doi.org/10.1101/19007294doi: medRxiv preprint
16
Amount of information1 Content of information2 Helpfulness of information3
Comparison Observations r p value r p value Odds ratio (95% CI) p value
Geneticists vs Paediatricians 142 0.03 0.679 0.07 0.232 2.25 (0.99 – 5.17) 0.05
Internet sites vs Paediatricians 182 0.34 < 0.001 0 0.96 1.88 (0.80 – 4.42) 0.144
Support groups vs Paediatricians 120 0.47 < 0.001 0.14 0.012 11.0 (1.42 – 85.20) 0.004
Internet sites vs Geneticists 360 0.32 < 0.001 0.12 0.035 2.5 (1.45 – 4.32) 0.001
Support groups vs Geneticists 252 0.51 < 0.001 0.29 < 0.001 21.0 (5.08 – 86.75) < 0.001
Support groups vs Internet sites 330 0.38 < 0.001 0.31 < 0.001 15.5 (3.71 – 64.77) < 0.001
Table 3. Comparative value of information from health professionals and non-professional sources. 1 Amount of information (too little; sufficient; too
much) and 2 Content of information (too complicated; clear and comprehendible; not relevant) was assessed by pairwise comparison of responses; 3
The helpfulness of information (helpful vs not helpful) was assessed by testing differences in paired proportions.
. CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted September 25, 2019. .https://doi.org/10.1101/19007294doi: medRxiv preprint
DISCUSSION
This is the first quantitative survey of its kind to investigate how parents experience the
communication of genomic tests for developmental disorders and their endeavours to gain
knowledge about health implications associated with their child’s diagnosis. At a time of rapid
advances in diagnosing rare disorders and diversification of genetics services, this is an
important topic. Our survey reveals parents have mixed experiences of attending genetics
services. A third of those in the UK reported dissatisfaction with the communication of test
results. Information provided by health specialists was less helpful and of inferior quality
compared to information respondents obtained from other sources, particularly voluntary
support groups. Information provided by health specialists was predominantly focused on
developmental and physical challenges typically present at diagnosis and parents relied
heavily on their own resources to find information about psychiatric manifestations
associated with their child’s genetic variant. Families in the UK were more reliant than the
USA on internet sites and voluntary sector organisations for information, particularly for
neurodevelopmental and psychiatric disorders.
The findings extend previous evidence showing that families often have difficulties obtaining
satisfactory information from clinical specialists to aid comprehension of genomic tests
results.[21–23] We have revealed new evidence concerning a broad range of genomic
disorders consistent with earlier findings concerning 22q11.2 deletion syndrome - one of the
most frequently diagnosed genomic disorders - in which parents predominantly obtained
psychiatric information from internet sites and support groups.[24,25] Consistent with studies
of rare disorders more generally, we found that most respondents resorted to internet
searches to help comprehend their child’s diagnosis.[26] However, many families do not
seek medical information online, and this may particularly be the case for more
socioeconomically deprived groups.[27] Limited access to information is associated with
increased stress and uncertainty for parents and negatively influences engagement with
healthcare services, potentially negating some the advantages of having precision
. CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted September 25, 2019. .https://doi.org/10.1101/19007294doi: medRxiv preprint
18
diagnoses.[28] Our survey did not gather sufficient demographic data to determine whether
hard-pressed families were less likely to seek online content. However, we are concerned
that socially disadvantaged families may not have the same degree of access to high quality
information, support and services to which they are entitled.[29] This is emphasised by our
finding that, as in previous studies, parents often consider information from clinical specialists
to be overcomplicated, irrelevant or unhelpful compared to online content or from support
groups.[30]
Our study showed that paediatric and genetic specialists tend to focus on providing
information about developmental and physical disabilities at the time of giving genetic test
results, suggesting either that information about psychiatric risks may be less readily
available, or that informing parents about risks of behavioural, emotional and psychotic
disorders is less relevant when communicating test results.[31–33] In the context of
communicating pathogenic neurodevelopmental CNVs with significant evidence of
psychiatric, our findings indicated parents were no more likely to be informed about these
than were others. Moreover, our findings suggest parents of children with ND-CNVs tend to
find psychiatric information through alternative sources including internet searches,
suggesting extensive evidence on neuropsychiatric genotype-phenotype associations in ND-
CNVs is yet to be incorporated into genetic counselling for individuals with developmental
disorders. Often cited concerns over overloading parents with information in the aftermath of
a genetic diagnosis should be balanced against the best interests of children and parents’
desires for comprehensive health information.[34–36] We recommend the translation of
evidence on adverse neuropsychiatric outcomes into care guidelines for ND-CNVs coupled
with mechanisms ensuring timely provision of family-oriented information which accounts for
the needs and wishes of families over time.[37–39]
Our findings revealed differences in the communication of test results and information
gathering between UK and US families. More than half of UK parents received their child’s
diagnosis from paediatricians, compared to one-in-five in the USA. Parents in the USA
. CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted September 25, 2019. .https://doi.org/10.1101/19007294doi: medRxiv preprint
19
received a broader range of medical and mental health information from their clinician,
whereas UK parents obtain most neurodevelopmental and psychiatric information from
alternative sources. However, the lower frequency of provision of psychiatric information by
clinicians the UK was not explained by the smaller proportion of parents receiving their result
from genetic specialists. As such, our survey failed to uncover evidence explaining why
provision of psychiatric information from clinical professionals is relatively infrequent the UK,
or, conversely why parents in US receive a broader range of information from their doctor.
Other factors may account for these differences, such as healthcare service models,
availability and duration of face-to-face appointments, or differences in professional
development and training.
Opinions vary on the benefits and risks of online health information, ranging from concerns
among health professionals over accuracy, relevance and under-regulation, to endorsements
from sociologists in support of its contribution to client empowerment. Although an
understudied topic, evidence has been published that the general public adopt contingent
behaviours towards online content, discriminating between trustworthy and untrustworthy
content in order to supplement rather than replace traditional media.[40] Importantly,
universal online search methods are increasingly concordant with the structure of internet
health information and the hierarchical nature of results created by popular search engines.
Therefore, we recommend initiatives which support clinicians to improve access to
comprehensive, high quality information around the time of diagnosis, including signposting
to digital content beyond traditional media and support voluntary support groups to innovate
new ways of supporting children with complex disabilities.
The findings presented here are timely; paediatric genetics services need to strike a fine
balance between delivering high quality services for escalating referrals and performing
increasingly sophisticated tests with lengthy consent procedures. That a significant
proportion of respondents in our survey expressed dissatisfaction receiving genetic
diagnoses highlights the challenge facing specialised clinical services. As the availability of
. CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted September 25, 2019. .https://doi.org/10.1101/19007294doi: medRxiv preprint
20
genomic testing in mainstream services increases, the demand for relevant patient-oriented
information concerning genetic influences on psychiatric risks are predicted to
increase.[41,42] However, informing patients and families about complex and uncertain
implications of genetic tests is challenging, requiring specialised expertise covering multiple
domains of physical, medical and mental health, sensitive risk counselling and facilitation of
parents’ adaptation to the diagnosis. Personalising psychiatric risk across the lifespan such
that families and patients understand the true nature of their risks is likely to become a
priority for psychiatrists and other specialists working in neuropsychiatric disorders. Without a
sound understanding of these risks, parents will be less well equipped to recognize and
respond to symptoms and access early interventions which – especially in the context of
psychotic disorders – can lead to better long term outcomes.[43,44] We recommend that
education and training in brain disorders is prioritised for all clinical specialties considering
genetic testing.[45,46] Curriculum content should be developed accordingly, ensuring genetic
counselling includes meaningful conversations about the full spectrum of medical and mental
health risks accompanied by contemporary, relevant information. Fortuitously, evidence
revealing complex but broadly similar psychiatric outcomes for children with recurrent
neurodevelopmental CNVs suggests integrating a coordinated general approach to
psychiatric care planning into a dedicated multidisciplinary clinical pathway for such children
could be justified, with individual tailoring for genotype-specific risks.[47] This would require
fundamental changes to service configuration and delivery and greater awareness of this
significant population among health providers and other professionals.
Our study has limitations. Recruitment was biased in favour of parents who engage with the
support groups who promoted the survey, potentially limiting the generalisability of our
findings. The survey was designed with broad accessibility in mind. However, online surveys
require significant internet literacy and time for participation, which may be difficult for some
families. Parents who readily access the internet, are, conceivably, more likely to use it for
seeking information related to the content of this study. The survey was overwhelmingly
. CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted September 25, 2019. .https://doi.org/10.1101/19007294doi: medRxiv preprint
21
completed by mothers. However, families with severely disabled children are rare and not
representative of the general population and this may be a reflection of the socio-domestic
influences on caregiving in the context of disability.[48] Also, we were unable to
independently verify health information provided by parents. Self-report surveys have
recognised shortcomings exacerbated by respondents potentially having to recall facts and
experiences several years after the event. Despite these limitations, the views and
experiences expressed by a large number of families provides a timely insight into the
current state of medical health information, clinical services and lay support for neuro-
disability communities.
In summary, our findings reveal that parents often feel inadequately informed by their clinical
specialists about potential neurodevelopmental and psychiatric challenges in the context of
paediatric genetic testing. Parents search extensively for information about their child’s
genetic diagnosis, retrieving neuropsychiatric information primarily from internet sites and lay
support groups, where accuracy and validity is unregulated and likely less reliable. We
believe the current results are important in informing service development and training in
both clinical genetics and psychiatry. In particular, they point to the need for closer
integration of medical genetics and psychiatry to address the needs of those receiving a
genetic diagnosis. Future initiatives should focus on identifying measures to promote the
inclusion of psychiatric risk information, provide greater support in genetic counselling clinics
and ensuring that education and training for practitioners encompass the full spectrum of
neurodevelopmental and mental health challenges faced by children with genomic disorders.
FIGURE LEGENDS
Figure 1. Comparative satisfaction with the delivery of genetic test results by genetic and
paediatric specialists. Upper panel (a): Parents’ satisfaction with how genetic test results
. CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted September 25, 2019. .https://doi.org/10.1101/19007294doi: medRxiv preprint
22
were communicated. Lower panel (b): Parents’ satisfaction with how genetic test results were
explained. UK (N = 188); USA (N = 85); All (N = 273). Chi-Square test for independence: * p
< 0.01; ** p < 0.001.
Figure 2. Variation in information sources for individual manifestations. Dot plots depicts
odds ratios for pairwise comparisons between sources first used for information about
recurrent CNV-associated manifestations compared with sources representative of three
major classes of disorder: (a) developmental disorders (intellectual disability [ID]); (b)
congenital disorders (cardiac defects); (c) neuropsychiatric disorders (autism spectrum
disorder). Sources: (i) health professionals – clinician at time of genetic diagnosis; clinician at
follow-up appointment; other health professional, (ii) other sources – internet sites; charity
support organisations (including Facebook groups); friends and family; books and leaflets.
Bars represent 95% confidence intervals. Manifestation groups: (i) developmental:
developmental delay (DD); intellectual disability (ID); speech and language delay (SLD), (ii)
physical: palatal defects; cardiac defects; seizures or epilepsy, (iii) neuropsychiatric: autism
spectrum disorder (ASD); attention deficit hyperactivity disorder (ADHD); obsessive
compulsive disorder (OCD); developmental coordination disorder (DCD), (iv) mood and
psychotic: schizophrenia or psychosis (psychotic); anxiety; depression.
Figure 3. Comparisons of information sources concerning developmental, physical and
psychiatric manifestations of genomic disorders reported by UK and USA respondents.
Manifestations were grouped into (a) developmental and physical; (b) neuropsychiatric; (c)
mood and psychotic; and (d) all combined (further defined in table 2). Information sources: (i)
Health professional – clinician at time of genetic diagnosis, clinician at follow-up, or other
health professional; (ii) Other – internet sites, charity support organisations (including
Facebook groups), friends and family, books and leaflets. Chi-Square test for independence:
* p < 0.001.
. CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted September 25, 2019. .https://doi.org/10.1101/19007294doi: medRxiv preprint
23
REFERENCES
1. Emerson E. Deprivation, ethnicity and the prevalence of intellectual and
developmental disabilities. J Epidemiol Community Health 2012;66:218–24.
2. Malhotra D, Sebat J. CNVs: harbingers of a rare variant revolution in psychiatric
genetics. Cell 2012;148:1223–41.
3. Cooper GM, Coe BP, Girirajan S, Rosenfeld JA, Vu TH, Baker C, Williams C, Stalker
H, Hamid R, Hannig V, Abdel-Hamid H, Bader P, McCracken E, Niyazov D, Leppig K,
Thiese H, Hummel M, Alexander N, Gorski J, Kussmann J, Shashi V, Johnson K,
Rehder C, Ballif BC, Shaffer LG, Eichler EE. A copy number variation morbidity map
of developmental delay. Nat Genet 2011;43:838–46.
4. Singh T, Walters JTR, Johnstone M, Curtis D, Suvisaari J, Torniainen M, Rees E,
Iyegbe C, Blackwood D, McIntosh AM, Kirov G, Geschwind D, Murray RM, Di Forti M,
Bramon E, Gandal M, Hultman CM, Sklar P, Palotie A, Sullivan PF, O’Donovan MC,
Owen MJ, Barrett JC. The contribution of rare variants to risk of schizophrenia in
individuals with and without intellectual disability. Nat Genet 2017;49:1167–73.
5. Schneider M, Debbané M, Bassett AS, Chow EWC, Fung WLA, Marianne B.M. van
den Bree MO, Murphy KC, Niarchou M, Kates WR, Antshel KM, Fremont W,
McDonald-McGinn DM, Gur RE, Zackai EH, Vorstman J, Duijff SN, Klaassen PWJ,
Swillen A, Gothelf D, Green T, Weizman A, Amelsvoort T Van, Evers L, Boot E,
Shashi V, Hooper SR, Bearden CE, Jalbrzikowski M, Marco Armando, Stefano Vicari
DGM, Ousley O, Campbell LE, Simon TJ, Stephan Eliez and for the IC on B and B in
22q11. . DS. Psychiatric Disorders From Childhood to Adulthood in 22q11.2 Deletion
Syndrome: Results From the International Consortium on Brain and Behavior in
22q11.2 Deletion Syndrome. Am J Psychiatry 2014;29:997–1003.
6. Monks S, Niarchou M, Davies AR, Walters JTR, Williams N, Owen MJ, van den Bree
. CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted September 25, 2019. .https://doi.org/10.1101/19007294doi: medRxiv preprint
24
MBM, Murphy KC. Further evidence for high rates of schizophrenia in 22q11.2
deletion syndrome. Schizophr Res 2014;153:231–6.
7. Niarchou M, Zammit S, van Goozen SHM, Thapar A, Tierling HM, Owen MJ, van den
Bree MBM. Psychopathology and cognition in children with 22q11.2 deletion
syndrome. Br J Psychiatry 2014:46–54.
8. Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP, Church DM,
Crolla J a., Eichler EE, Epstein CJ, Faucett WA, Feuk L, Friedman JM, Hamosh A,
Jackson L, Kaminsky EB, Kok K, Krantz ID, Kuhn RM, Lee C, Ostell JM, Rosenberg
C, Scherer SW, Spinner NB, Stavropoulos DJ, Tepperberg JH, Thorland EC,
Vermeesch JR, Waggoner DJ, Watson MS, Martin CL, Ledbetter DH. Consensus
Statement: Chromosomal Microarray Is a First-Tier Clinical Diagnostic Test for
Individuals with Developmental Disabilities or Congenital Anomalies. Am J Hum Genet
2010;86:749–64.
9. Deciphering Developmental Disorders Study. Prevalence and architecture of de novo
mutations in developmental disorders. Nature 2017;542:433–7.
10. Kirov G, Rees E, Walters JTR, Escott-Price V, Georgieva L, Richards AL, Chambert
KD, Davies G, Legge SE, Moran JL, McCarroll S a, O’Donovan MC, Owen MJ. The
Penetrance of Copy Number Variations for Schizophrenia and Developmental Delay.
Biol Psychiatry 2013;75:378–85.
11. Rees E, Kendall K, Pardiñas AF, Legge SE, Pocklington A, Escott-price V, Maccabe
JH, Collier DA, Holmans P, Donovan MCO, Owen MJ, Walters JTR, Kirov G. Analysis
of Intellectual Disability Copy Number Variants for Association With Schizophrenia.
JAMA Psychiatry 2016;73:1–7.
12. Owen MJ, O’Donovan MC, Thapar A, Craddock N. Neurodevelopmental hypothesis of
schizophrenia. Br J Psychiatry 2011;198(3):173–5.
13. Bouwkamp CG, Kievit AJA, Markx S, Friedman JI, Van Zutven L, Van Minkelen R,
. CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted September 25, 2019. .https://doi.org/10.1101/19007294doi: medRxiv preprint
25
Vrijenhoek T, Xu B, Sterrenburg-Van De Nieuwegiessen I, Veltman JA, Bonifati V,
Kushner SA. Copy number variation in syndromic forms of psychiatric illness: The
emerging value of clinical genetic testing in psychiatry. Am J Psychiatry
2017;174:1036–50.
14. Wright CF, Fitzgerald TW, Jones WD, Clayton S, McRae JF, Van Kogelenberg M,
King DA, Ambridge K, Barrett DM, Bayzetinova T, Bevan AP, Bragin E, Chatzimichali
EA, Gribble S, Jones P, Krishnappa N, Mason LE, Miller R, Morley KI, Parthiban V,
Prigmore E, Rajan D, Sifrim A, Swaminathan GJ, Tivey AR, Middleton A, Parker M,
Carter NP, Barrett JC, Hurles ME, Fitzpatrick DR, Firth H V. Genetic diagnosis of
developmental disorders in the DDD study: A scalable analysis of genome-wide
research data. Lancet 2015;385:1305–14.
15. Slade I, Subramanian DN, Burton H. Genomics education for medical professionals -
the current UK landscape. Clin Med 2016;16:347–52.
16. Burton H, Cole T, Lucassen AM. Genomic medicine : challenges and opportunities for
physicians The impact of genomic technologies on diagnosis. Clin Med 2012;12:416–
9.
17. Dheensa S, Lucassen A, Fenwick A. Fostering trust in healthcare: Participants’
experiences, views, and concerns about the 100,000 genomes project. Eur J Med
Genet 2018;62:335–41.
18. Limb L, Nutt S. Improving Lives, Optimising Resources : A Vision for the UK Rare
Disease Strategy. 2011. Available from https://www.raredisease.org.uk/wp-
content/uploads/sites/7/2018/04/improving-lives-optmising-resources-a-vision-for-the-
uk-rare-disease-strategy.pdf.
19. Wright CF, FitzPatrick DR, Firth H V. Paediatric genomics: Diagnosing rare disease in
children. Nat Rev Genet 2018;19:253–68.
20. Ryten M, Owen M, Kirov G, Cuthbert A, Saklavata J, Simpson M, Treacy B,
. CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted September 25, 2019. .https://doi.org/10.1101/19007294doi: medRxiv preprint
26
Mohammed S. Provision of clinical genetic tests within the NHS associated with
Mental Health Disorders. UK Genetic Testing Network Brief Report 2016. Available
from:
https://ukgtn.nhs.uk/fileadmin/uploads/ukgtn/Documents/Resources/Library/Reports_
Guidelines/Dec-Mental_Health_Briefing_Report_FINAL.pdf
21. Ashtiani S, Makela N, Carrion P, Austin J. Parents’ experiences of receiving their
child’s genetic diagnosis: A qualitative study to inform clinical genetics practice. Am J
Med Genet 2014;164:1496–502.
22. Maya I, Sharony R, Yacobson S, Kahana S, Yeshaya J, Tenne T, Agmon-Fishman I,
Cohen-Vig L, Goldberg Y, Berger R, Basel-Salmon L, Shohat M. When genotype is
not predictive of phenotype: Implications for genetic counseling based on 21,594
chromosomal microarray analysis examinations. Genet Med 2018;20:128–31.
23. Reiff M, Bernhardt BA, Mulchandani S, Soucier D, Cornell D, Pyeritz RE, Spinner NB.
“What does it mean?”: Uncertainties in understanding results of chromosomal
microarray testing. Genet Med 2012;14:250–8.
24. Hercher L, Bruenner G. Living with a child at risk for psychotic illness: The experience
of parents coping with 22q11 deletion syndrome: An exploratory study. Am J Med
Genet 2008;146:2355–60.
25. van den Bree MBM, Miller G, Mansell E, Thapar A, Flinter F, Owen MJ. The internet is
parents’ main source of information about psychiatric manifestations of 22q11.2
deletion syndrome (22q11.2DS). Eur J Med Genet 2013;56:439–41.
26. Nicholl H, Tracey C, Begley T, King C, Lynch AM. Internet Use by Parents of Children
With Rare Conditions: Findings From a Study on Parents’ Web Information Needs.
Eysenbach G, editor. J Med Internet Res 2017;19:e51.
27. Roche MI, Skinner D. How parents search, interpret, and evaluate genetic information
obtained from the internet. J Genet Couns 2009;18:119–29.
. CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted September 25, 2019. .https://doi.org/10.1101/19007294doi: medRxiv preprint
27
28. Goodwin J, Schoch K, Shashi V, Hooper SR, Morad O, Zalevsky M, Gothelf D,
Campbell LE. A tale worth telling: the impact of the diagnosis experience on disclosure
of genetic disorders. J Intellect Disabil Res 2014;59:474–86.
29. Ramsey I, Corsini N, Peters MDJ, Eckert M. A rapid review of consumer health
information needs and preferences. Patient Educ Couns 2017;100:1634–42.
30. Gilmore L. Supporting families of children with rare and unique chromosome
disorders. Res Pract Intellect Dev Disabil 2018;5:8–16.
31. Baughman ST, Morris E, Jensen K, Austin J. Disclosure of psychiatric manifestations
of 22q11.2 deletion syndrome in medical genetics: A 12-year retrospective chart
review. Am J Med Genet 2015;167:2650–56.
32. Martin M, Mikhaelian M, Cytrynbaum, Shuman C, Chitayat DA, Weksberg R. 22q11.2
Deletion Syndrome: Attitudes towards Disclosing the Risk of Psychiatric Illness. J
Genet Couns 2012;21:825–34.
33. Morris E, Inglis A, Friedman J, Austin J. Discussing the psychiatric manifestations of
22q11.2 deletion syndrome: An exploration of clinical practice among medical
geneticists. Genet Med 2013;15:713–20.
34. Walser SA, Kellom KS, Palmer SC, Bernhardt BA. Comparing genetic counselor’s and
patient’s perceptions of needs in prenatal chromosomal microarray testing. Prenat
Diagn 2015;35:870–8.
35. Dondorp W, Sikkema-Raddatz B, de Die-Smulders C, de Wert G. Arrays in postnatal
and prenatal diagnosis: An exploration of the ethics of consent. Hum Mutat
2012;33:916–22.
36. Merrill SL, Guthrie KJ. Is it Time for Genomic Counseling? Retrofitting Genetic
Counseling for the Era of Genomic Medicine. Curr Genet Med Rep 2015;3:57–64.
37. Hart SJ, Schoch K, Shashi V, Callanan N. Communication of Psychiatric Risk in
22q11.2 Deletion Syndrome: A Pilot Project. J Genet Couns 2016;25:6–17.
. CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted September 25, 2019. .https://doi.org/10.1101/19007294doi: medRxiv preprint
28
38. Costain G, Chow EWC, Ray PN, Bassett AS. Caregiver and adult patient perspectives
on the importance of a diagnosis of 22q11.2 deletion syndrome. J Intellect Disabil Res
2012;56:641–51.
39. Bassett AS, McDonald-McGinn DM, Devriendt K, Digilio MC, Goldenberg P, Habel A,
Marino B, Oskarsdottir S, Philip N, Sullivan K, Swillen A, Vorstman J, Anne S. Bassett,
Donna M. McDonald-McGinn, Koen Devriendt, Maria Cristina Digilio, Paula
Goldenberg, MSW, Alex Habel, Bruno Marino, Solveig Oskarsdottir, Nicole Philip,
Kathleen Sullivan, Ann Swillen JV, Bassett AS, McDonald-McGinn DM, Devriendt K,
Digilio MC, Goldenberg P, Habel A, Marino B, Oskarsdottir S, Philip N, Sullivan K,
Swillen A, Vorstman J. Practical Guidelines for Managing Patients with 22q11.2
Deletion Syndrome. J Pediatr 2011;159:332–39.
40. Nettleton S, Burrows R, O’Malley L. The mundane realities of the everyday lay use of
the internet for health, and their consequences for media convergence. Sociol Heal Illn
2005;27:972–92.
41. Wolfe K, Stueber K, McQuillin A, Jichi F, Patch C, Flinter F, Strydom A, Bass N.
Genetic testing in intellectual disability psychiatry: Opinions and practices of UK child
and intellectual disability psychiatrists. J Appl Res Intellect Disabil 2018;31:273–84.
42. Baker K, Costain G, Fung WLA, Bassett AS. Chromosomal microarray analysis - a
routine clinical genetic test for patients with schizophrenia. Lancet Psychiatry
2014;1:329–31.
43. Onwumere J, Bebbington P, Kuipers E. Family interventions in early psychosis:
specificity and effectiveness. Epidemiol Psychiatr Sci 2011;20:113–9.
44. Valmaggia R, K McGuire P, Fusar-Poli P, Howes O, McCrone P. Economic Impact of
Early Detection and Early Intervention of Psychosis. Curr Pharm Des 2012;18:592–5.
45. O’Donovan MC, Owen MJ. The implications of the shared genetics of psychiatric
disorders. Nat Med 2016;22:1214–19.
. CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted September 25, 2019. .https://doi.org/10.1101/19007294doi: medRxiv preprint
29
46. Hall J, Owen MJ. Psychiatric classification - A developmental perspective. Br J
Psychiatry 2015;207:281–2.
47. Chawner SJRA, Owen MJ, Holmans P, Raymond FL, Skuse D, Hall J, van den Bree
MBM. Genotype–phenotype associations in children with copy number variants
associated with high neuropsychiatric risk in the UK (IMAGINE-ID): a case-control
cohort study. Lancet Psychiatry 2019;6:493–505.
48. Sharma N, Chakrabarti S, Grover S. Gender differences in caregiving among family -
caregivers of people with mental illnesses. World J Psychiatry 2016;6:7–17.
ACKNOWLEDGEMENTS
We are grateful to all the families who helped with this study. We thank Dr Beverley Searle
and all the staff at the charity Unique - Understanding Rare Chromosome and Gene
Disorders, for their support and for promoting the study. We also wish to thank Max Appeal
for their assistance with the advertising the survey. We are grateful to Dr Michael Arribas
Ayllon (School of Social Sciences, Cardiff University) for his valuable contribution. The work
was supported by The Waterloo Foundation (Grant No. 506926) and the Medical Research
Council (Grant No. MR/N022572/1). The funders had no role in the study design, data
collection, analysis and interpretation of findings and made no contribution to writing the
report. All authors had full access to all the data collected in the survey. The corresponding
author had final responsibility for the decision to submit for publication.
. CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted September 25, 2019. .https://doi.org/10.1101/19007294doi: medRxiv preprint
Figure 1.
. CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted September 25, 2019. .https://doi.org/10.1101/19007294doi: medRxiv preprint
Figure 2.
. CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted September 25, 2019. .https://doi.org/10.1101/19007294doi: medRxiv preprint
Figure 3.
. CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted September 25, 2019. .https://doi.org/10.1101/19007294doi: medRxiv preprint
Top Related